Micrometer-scale tPA beads amplify plasmin generation for enhanced thrombolytic therapy.

ABSTRACT: Rapid restoration of blood flow is critical in treating acute ischemic stroke. Current thrombolytic therapies using tissue plasminogen activator (tPA) are limited by low recanalization rates and risks of off-target bleeding. Here, we demonstrate that a remarkably simple adjustment-using micrometer-scale rather than sub-micrometer particles to immobilize tPA-fundamentally improves thrombolysis. By merely increasing the particle diameter from 0.1 to 1.0 μm, we achieve a dramatic shift in lysis dynamics: 1.0 μm tPA-beads generate higher plasmin flux, readily overcome antiplasmin inhibition, and trigger a self-propagating cascade of fibrinolysis. This leads to near-complete clot dissolution at tPA doses nearly 100-fold lower than standard free tPA, both in vitro and in a murine model of acute

SUBMITTER: Osmond MJ 

PROVIDER: S-EPMC12284430 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature